Resuscitators' opinions on using a respiratory function monitor during neonatal resuscitation.

AIM: The aim of this study was to assess the resuscitators' opinions of the usefulness and clinical value of using a respiratory function monitor (RFM) when resuscitating extremely preterm infants with positive pressure ventilation. METHODS: The link to an online survey was sent to 106 resuscitators from six countries who were involved in a multicentre trial that compared the percentage of inflations within a predefined target range with and without the RFM. The resuscitators were asked to assess the usefulness and clinical value of the RFM. The survey was online for 4 months after the trial ended in May 2019. RESULTS: The survey was completed by 74 (70%) resuscitators of which 99% considered the RFM to be helpful during neonatal resuscitation and 92% indicated that it influenced their decision-making. The majority (76%) indicated that using the RFM improved their practice and made resuscitation more effective, even when the RFM was not available. Inadequate training was the key issue that limited the effectiveness of the RFM: 45% felt insufficiently trained, and 78% felt more training in using and interpreting the RFM would have been beneficial. CONCLUSION: Resuscitators considered the RFM to be helpful to guide neonatal resuscitation, but sufficient training was required to achieve the maximum benefit.

Computational analysis of neonatal ventilator waveforms and loops.

BACKGROUND: Modern neonatal ventilators allow the downloading of their data with a high sampling rate. We wanted to develop an algorithm that automatically recognises and characterises ventilator inflations from ventilator pressure and flow data. METHODS: We downloaded airway pressure and flow data with 100 Hz sampling rate from Dräger Babylog VN500 ventilators ventilating critically ill infants. We developed an open source Python package, Ventiliser, that includes a rule-based algorithm to automatically discretise ventilator data into a sequence of flow and pressure states and to recognise ventilator inflations and an information gain approach to identify inflation phases (inspiration, expiration) and sub-phases (pressure rise, pressure plateau, inspiratory hold etc.). RESULTS: Ventiliser runs on a personal computer and analyses 24 h of ventilation in 2 min. With longer recordings, the processing time increases linearly. It generates a table reporting indices of each breath and its sub-phases. Ventiliser also allows visualisation of individual inflations as waveforms or loops. Ventiliser identified >97% of ventilator inflations and their sub-phases in an out-of-sample validation of manually annotated data. We also present detailed quantitative analysis and comparison of two 1-hour-long ventilation periods. CONCLUSIONS: Ventiliser can analyse ventilation patterns and ventilator-patient interactions over long periods of mechanical ventilation. IMPACT: We have developed a computational method to recognize and analyse ventilator inflations from raw data downloaded from ventilators of preterm and critically ill infants. There have been no previous reports on the computational analysis of neonatal ventilator data. We have made our program, Ventiliser, freely available. Clinicians and researchers can use Ventiliser to analyse ventilator inflations, waveforms and loops over long periods. Ventiliser can also be used to study ventilator-patient interactions.

Sustained versus standard inflations during neonatal resuscitation to prevent mortality and improve respiratory outcomes.

BACKGROUND: At birth, infants' lungs are fluid-filled. For newborns to have a successful transition, this fluid must be replaced by air to enable gas exchange. Some infants are judged to have inadequate breathing at birth and are resuscitated with positive pressure ventilation (PPV). Giving prolonged (sustained) inflations at the start of PPV may help clear lung fluid and establish gas volume within the lungs. OBJECTIVES: To assess the benefits and harms of an initial sustained lung inflation (SLI) (> 1 second duration) versus standard inflations (≤ 1 second) in newborn infants receiving resuscitation with intermittent PPV. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 3), MEDLINE via PubMed (1966 to 1 April 2019), Embase (1980 to 1 April 2019), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 1 April 2019). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles to identify randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing initial sustained lung inflation (SLI) versus standard inflations given to infants receiving resuscitation with PPV at birth. DATA COLLECTION AND ANALYSIS: We assessed the methodological quality of included trials using Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria (assessing randomisation, blinding, loss to follow-up, and handling of outcome data). We evaluated treatment effects using a fixed-effect model with risk ratio (RR) for categorical data; and mean standard deviation (SD), and weighted mean difference (WMD) for continuous data. We used the GRADE approach to assess the quality of evidence. MAIN RESULTS: Ten trials enrolling 1467 infants met our inclusion criteria. Investigators in nine trials (1458 infants) administered sustained inflation with no chest compressions. Use of sustained inflation had no impact on the primary outcomes of this review: mortality in the delivery room (typical RR 2.66, 95% confidence interval (CI) 0.11 to 63.40 (I² not applicable); typical RD 0.00, 95% CI -0.02 to 0.02; I² = 0%; 5 studies, 479 participants); and mortality during hospitalisation (typical RR 1.09, 95% CI 0.83 to 1.43; I² = 42%; typical RD 0.01, 95% CI -0.02 to 0.04; I² = 24%; 9 studies, 1458 participants). The quality of the evidence was low for death in the delivery room because of limitations in study design and imprecision of estimates (only one death was recorded across studies). For death before discharge the quality was moderate: with longer follow-up there were more deaths (n = 143) but limitations in study design remained. Among secondary outcomes, duration of mechanical ventilation was shorter in the SLI group (mean difference (MD) -5.37 days, 95% CI -6.31 to -4.43; I² = 95%; 5 studies, 524 participants; low-quality evidence). Heterogeneity, statistical significance, and magnitude of effects of this outcome are largely influenced by a single study at high risk of bias: when this study was removed from the analysis, the size of the effect was reduced (MD -1.71 days, 95% CI -3.04 to -0.39; I² = 0%). Results revealed no differences in any of the other secondary outcomes (e.g. risk of endotracheal intubation outside the delivery room by 72 hours of age (typical RR 0.91, 95% CI 0.79 to 1.04; I² = 65%; 5 studies, 811 participants); risk of surfactant administration during hospital admission (typical RR 0.99, 95% CI 0.91 to 1.08; I² = 0%; 9 studies, 1458 participants); risk of chronic lung disease (typical RR 0.99, 95% CI 0.83 to 1.18; I² = 0%; 4 studies, 735 participants); pneumothorax (typical RR 0.89, 95% CI 0.57 to 1.40; I² = 34%; 8 studies, 1377 infants); or risk of patent ductus arteriosus requiring pharmacological treatment (typical RR 0.99, 95% CI 0.87 to 1.12; I² = 48%; 7 studies, 1127 infants). The quality of evidence for these secondary outcomes was moderate (limitations in study design ‒ GRADE) except for pneumothorax (low quality: limitations in study design and imprecision of estimates ‒ GRADE). We could not perform any meta-analysis in the comparison of the use of initial sustained inflation versus standard inflations in newborns receiving resuscitation with chest compressions because we identified only one trial for inclusion (a pilot study of nine preterm infants). AUTHORS' CONCLUSIONS: Our meta-analysis of nine studies shows that sustained lung inflation without chest compression was not better than intermittent ventilation for reducing mortality in the delivery room (low-quality evidence ‒ GRADE) or during hospitalisation (moderate-quality evidence ‒ GRADE), which were the primary outcomes of this review. However, the single largest study, which was well conducted and had the greatest number of enrolled infants, was stopped early for higher mortality rate in the sustained inflation group. When considering secondary outcomes, such as rate of intubation, rate or duration of respiratory support, or bronchopulmonary dysplasia, we found no benefit of sustained inflation over intermittent ventilation (moderate-quality evidence ‒ GRADE). Duration of mechanical ventilation was shortened in the SLI group (low-quality evidence ‒ GRADE); this result should be interpreted cautiously, however, as it might have been influenced by study characteristics other than the intervention. There is no evidence to support the use of sustained inflation based on evidence from our review.

Leak Compensation During Volume Guarantee With the Dräger Babylog VN500 Neonatal Ventilator.

OBJECTIVES: To investigate how compensating for endotracheal tube leaks by targeting the leak-compensated tidal volume affects measured physiologic and ventilator variables during neonatal mechanical ventilation. DESIGN: Retrospective observational study. SETTING: A level III Neonatal ICU. PATIENTS: We enrolled 30 neonates who were ventilated using synchronized intermittent positive pressure mode with volume guarantee and had at least 12 hours of continuous detailed recording of ventilation variables. INTERVENTIONS: Infants were treated using the Dräger VN500 ventilator (Dräger, Lübeck, Germany), which uses a proprietary algorithm to measure and compensate for endotracheal tube leaks. Eleven were ventilated without leak compensation and 19 with leak compensation. MEASUREMENTS AND MAIN RESULTS: Detailed ventilation data were collected and analyzed at 1 Hz, with intermittent blood gas values. The percentage of leak was less than 20% in 73% of leak-compensated inflations, and the volume of the leak compensation was less than 1 mL/kg in 97.3% of inflations. Between the two groups, ventilation variables were comparable, except the percentage of leak that was significantly (p = 0.005) higher in the recordings with leak compensation. Without leak compensation, the mean expired tidal volume was maintained very close to the set level up to 50% leak, but with leaks greater than 50%, it declined progressively. With leak compensation, the mean leak-compensated expired tidal volume was well maintained even with leak greater than 90% although with large variability. Without leak compensation, the difference between the maximum allowed inflating pressure and the peak inflating pressure decreased progressively as the leak increased. This did not occur with leak compensation. The median PCO2 was slightly higher with leak compensation. CONCLUSIONS: During volume guarantee ventilation with a Dräger VN500 ventilator, without leak compensation the expired tidal volume declined after 50% leak. With leak compensation, the tidal volume was maintained even with a large leak. With leak compensation, there was a more stable peak inflating pressure, although the PCO2 was slightly higher.

Association Between Oxygen Saturation Targeting and Death or Disability in Extremely Preterm Infants in the Neonatal Oxygenation Prospective Meta-analysis Collaboration.

Importance: There are potential benefits and harms of hyperoxemia and hypoxemia for extremely preterm infants receiving more vs less supplemental oxygen. Objective: To compare the effects of different target ranges for oxygen saturation as measured by pulse oximetry (Spo2) on death or major morbidity. Design, Setting, and Participants: Prospectively planned meta-analysis of individual participant data from 5 randomized clinical trials (conducted from 2005-2014) enrolling infants born before 28 weeks' gestation. Exposures: Spo2 target range that was lower (85%-89%) vs higher (91%-95%). Main Outcomes and Measures: The primary outcome was a composite of death or major disability (bilateral blindness, deafness, cerebral palsy diagnosed as ≥2 level on the Gross Motor Function Classification System, or Bayley-III cognitive or language score <85) at a corrected age of 18 to 24 months. There were 16 secondary outcomes including the components of the primary outcome and other major morbidities. Results: A total of 4965 infants were randomized (2480 to the lower Spo2 target range and 2485 to the higher Spo2 range) and had a median gestational age of 26 weeks (interquartile range, 25-27 weeks) and a mean birth weight of 832 g (SD, 190 g). The primary outcome occurred in 1191 of 2228 infants (53.5%) in the lower Spo2 target group and 1150 of 2229 infants (51.6%) in the higher Spo2 target group (risk difference, 1.7% [95% CI, -1.3% to 4.6%]; relative risk [RR], 1.04 [95% CI, 0.98 to 1.09], P = .21). Of the 16 secondary outcomes, 11 were null, 2 significantly favored the lower Spo2 target group, and 3 significantly favored the higher Spo2 target group. Death occurred in 484 of 2433 infants (19.9%) in the lower Spo2 target group and 418 of 2440 infants (17.1%) in the higher Spo2 target group (risk difference, 2.8% [95% CI, 0.6% to 5.0%]; RR, 1.17 [95% CI, 1.04 to 1.31], P = .01). Treatment for retinopathy of prematurity was administered to 220 of 2020 infants (10.9%) in the lower Spo2 target group and 308 of 2065 infants (14.9%) in the higher Spo2 target group (risk difference, -4.0% [95% CI, -6.1% to -2.0%]; RR, 0.74 [95% CI, 0.63 to 0.86], P < .001). Severe necrotizing enterocolitis occurred in 227 of 2464 infants (9.2%) in the lower Spo2 target group and 170 of 2465 infants (6.9%) in the higher Spo2 target group (risk difference, 2.3% [95% CI, 0.8% to 3.8%]; RR, 1.33 [95% CI, 1.10 to 1.61], P = .003). Conclusions and Relevance: In this prospectively planned meta-analysis of individual participant data from extremely preterm infants, there was no significant difference between a lower Spo2 target range compared with a higher Spo2 target range on the primary composite outcome of death or major disability at a corrected age of 18 to 24 months. The lower Spo2 target range was associated with a higher risk of death and necrotizing enterocolitis, but a lower risk of retinopathy of prematurity treatment.

Volume-targeted versus pressure-limited ventilation in neonates.

BACKGROUND: Damage caused by lung overdistension (volutrauma) has been implicated in the development of bronchopulmonary dysplasia (BPD). Modern neonatal ventilation modes can target a set tidal volume as an alternative to traditional pressure-limited ventilation (PLV) using a fixed inflation pressure. Volume-targeted ventilation (VTV) aims to produce a more stable tidal volume in order to reduce lung damage and stabilise the partial pressure of carbon dioxide (pCO2). OBJECTIVES: To determine whether VTV compared with PLV leads to reduced rates of death and death or BPD in newborn infants and to determine whether use of VTV affected outcomes including air leak, cranial ultrasound findings and neurodevelopment. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 12), MEDLINE via PubMed (1966 to 13 January 2017), Embase (1980 to 13 January 2017) and CINAHL (1982 to 13 January 2017). We also searched clinical trials databases, conference proceedings and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We contacted the principal investigators of studies to obtain supplementary information. SELECTION CRITERIA: Randomised and quasi-randomised trials comparing VTV versus PLV in infants of less than 44 weeks' postmenstrual age and reporting clinically relevant outcomes. DATA COLLECTION AND ANALYSIS: We assessed risk of bias for each trial using Cochrane methodology. We evaluated quality of evidence for each outcome using GRADE criteria. We tabulated mortality, rates of BPD, short-term clinical outcomes and long-term developmental outcomes. STATISTICS: for categorical outcomes, we calculated typical estimates for risk ratios (RR), risk differences (RD) and number needed to treat for an additional beneficial outcome (NNTB). For continuous variables, we calculated typical estimates for mean differences (MD). We used 95% confidence intervals (CI) and assumed a fixed-effect model for meta-analysis. MAIN RESULTS: Twenty randomised trials met our inclusion criteria; 16 parallel trials (977 infants) and four cross-over trials (88 infants). No studies were blinded and the quality of evidence for outcomes assessed varied from moderate to low.We found no difference in the primary outcome, death before hospital discharge, between VTV modes versus PLV modes (typical RR 0.75, 95% CI 0.53 to 1.07; low quality evidence). However, there was moderate quality evidence that the use of VTV modes resulted in a reduction in the primary outcome, death or BPD at 36 weeks' gestation (typical RR 0.73, 95% CI 0.59 to 0.89; typical NNTB 8, 95% CI 5 to 20) and the following secondary outcomes: rates of pneumothorax (typical RR 0.52, 95% CI 0.31 to 0.87; typical NNTB 20, 95% CI 11 to 100), mean days of mechanical ventilation (MD -1.35 days, 95% CI -1.83 to -0.86), rates of hypocarbia (typical RR 0.49, 95% CI 0.33 to 0.72; typical NNTB 3, 95% CI 2 to 5), rates of grade 3 or 4 intraventricular haemorrhage (typical RR 0.53, 95% CI 0.37 to 0.77; typical NNTB 11, 95% CI 7 to 25) and the combined outcome of periventricular leukomalacia with or without grade 3 or 4 intraventricular haemorrhage (typical RR 0.47, 95% CI 0.27 to 0.80; typical NNTB 11, 95% CI 7 to 33). VTV modes were not associated with any increased adverse outcomes. AUTHORS' CONCLUSIONS: Infants ventilated using VTV modes had reduced rates of death or BPD, pneumothoraces, hypocarbia, severe cranial ultrasound pathologies and duration of ventilation compared with infants ventilated using PLV modes. Further studies are needed to identify whether VTV modes improve neurodevelopmental outcomes and to compare and refine VTV strategies.

Sustained versus standard inflations during neonatal resuscitation to prevent mortality and improve respiratory outcomes.

BACKGROUND: At birth, infants' lungs are fluid-filled. For newborns to have a successful transition, this fluid must be replaced by air to enable effective breathing. Some infants are judged to have inadequate breathing at birth and are resuscitated with positive pressure ventilation (PPV). Giving prolonged (sustained) inflations at the start of PPV may help clear lung fluid and establish gas volume within the lungs. OBJECTIVES: To assess the efficacy of an initial sustained (> 1 second duration) lung inflation versus standard inflations (≤ 1 second) in newly born infants receiving resuscitation with intermittent PPV. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 1), MEDLINE via PubMed (1966 to 17 February 2017), Embase (1980 to 17 February 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 17 February 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles to identify randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing initial sustained lung inflation (SLI) versus standard inflations given to infants receiving resuscitation with PPV at birth. DATA COLLECTION AND ANALYSIS: We assessed the methodological quality of included trials using Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria (assessing randomisation, blinding, loss to follow-up, and handling of outcome data). We evaluated treatment effects using a fixed-effect model with risk ratio (RR) for categorical data and mean, standard deviation (SD), and weighted mean difference (WMD) for continuous data. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. MAIN RESULTS: Eight trials enrolling 941 infants met our inclusion criteria. Investigators in seven trials (932 infants) administered sustained inflation with no chest compressions. Use of sustained inflation had no impact on the primary outcomes of this review - mortality in the delivery room (typical RR 2.66, 95% confidence interval (CI) 0.11 to 63.40; participants = 479; studies = 5; I² not applicable) and mortality during hospitalisation (typical RR 1.01, 95% CI 0.67 to 1.51; participants = 932; studies = 7; I² = 19%); the quality of the evidence was low for death in the delivery room (limitations in study design and imprecision of estimates) and was moderate for death before discharge (limitations in study design of most included trials). Amongst secondary outcomes, duration of mechanical ventilation was shorter in the SLI group (mean difference (MD) -5.37 days, 95% CI -6.31 to -4.43; participants = 524; studies = 5; I² = 95%; low-quality evidence). Heterogeneity, statistical significance, and magnitude of effects of this outcome are largely influenced by a single study: When this study was removed from the analysis, the effect was largely reduced (MD -1.71 days, 95% CI -3.04 to -0.39, I² = 0%). Results revealed no differences in any of the other secondary outcomes (e.g. rate of endotracheal intubation outside the delivery room by 72 hours of age (typical RR 0.93, 95% CI 0.79 to 1.09; participants = 811; studies = 5; I² = 0%); need for surfactant administration during hospital admission (typical RR 0.97, 95% CI 0.86 to 1.10; participants = 932; studies = 7; I² = 0%); rate of chronic lung disease (typical RR 0.95, 95% CI 0.74 to 1.22; participants = 683; studies = 5; I² = 47%); pneumothorax (typical RR 1.44, 95% CI 0.76 to 2.72; studies = 6, 851 infants; I² = 26%); or rate of patent ductus arteriosus requiring pharmacological treatment (typical RR 1.08, 95% CI 0.90 to 1.30; studies = 6, 745 infants; I² = 36%). The quality of evidence for these secondary outcomes was moderate (limitations in study design of most included trials - GRADE) except for pneumothorax (low quality: limitations in study design and imprecision of estimates - GRADE). AUTHORS' CONCLUSIONS: Sustained inflation was not better than intermittent ventilation for reducing mortality in the delivery room and during hospitalisation. The number of events across trials was limited, so differences cannot be excluded. When considering secondary outcomes, such as need for intubation, need for or duration of respiratory support, or bronchopulmonary dysplasia, we found no evidence of relevant benefit for sustained inflation over intermittent ventilation. The duration of mechanical ventilation was shortened in the SLI group. This result should be interpreted cautiously, as it can be influenced by study characteristics other than the intervention. Future RCTs should aim to enrol infants who are at higher risk of morbidity and mortality, should stratify participants by gestational age, and should provide more detailed monitoring of the procedure, including measurements of lung volume and presence of apnoea before or during the SLI.

Sustained versus standard inflations during neonatal resuscitation to prevent mortality and improve respiratory outcomes.

BACKGROUND: At birth, infants' lungs are fluid-filled; this fluid must be replaced by air to allow for effective breathing. Some infants are judged to have inadequate breathing at birth and are resuscitated with positive pressure ventilation (PPV). Giving prolonged (sustained) inflations at the start of PPV may help clear lung fluid and establish gas volume in the lungs. OBJECTIVES: To assess the efficacy of initial sustained (> one second duration) lung inflation compared to standard inflations (≤ one second) in newly born infants receiving resuscitation with intermittent PPV. SEARCH METHODS: We searched on PubMed (1966 to 1 February 2015), EMBASE (1980 to 1 February 2015) and the Cochrane Central Register of Controlled Trials (the Cochrane Library 2015). No language restrictions were applied. We searched the abstracts of the Pediatric Academic Societies (PAS) from 2000 to 2014. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing giving initial sustained lung inflations (SLI) vs. standard inflations to infants receiving resuscitation with PPV at birth. DATA COLLECTION AND ANALYSIS: We assessed methodological quality of the included trials using Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria (assessing randomisation, blinding, loss to follow-up and handling of outcome data). We evaluated the treatment effect using a fixed-effect model using risk ratio for categorical data and using mean, standard deviation (SD) and weighted mean difference (WMD) for continuous data. MAIN RESULTS: Two trials enrolling 352 infants met our inclusion criteria. There were no differences in the rates of mortality during hospitalisation (RR 1.59, 95% CI 0.81 to 3.10; two trials, 352 infants), intubation in the first three days of life (RR 0.85, 95% CI 0.72 to 1.02; two trials, 352 infants) or chronic lung disease (RR 1.06, 95% CI 0.79 to 1.42; two trials, 349 infants) between infants who received sustained versus standard inflations. The rate of patent ductus arteriosus (reported as need for pharmacological treatment) was higher in the sustained inflation group (RR 1.27, 95% CI 1.03 to 1.56; two trials, 352 infants). AUTHORS' CONCLUSIONS: At present there is insufficient evidence from clinical trials to determine the efficacy and safety of initial sustained lung inflation for newborn infants resuscitated with PPV. RCTs comparing PPV with and without sustained inflations at neonatal resuscitation are warranted.

Delaying cord clamping until ventilation onset improves cardiovascular function at birth in preterm lambs.

Delayed cord clamping improves circulatory stability in preterm infants at birth, but the underlying physiology is unclear. We investigated the effects of umbilical cord clamping, before and after ventilation onset, on cardiovascular function at birth. Prenatal surgery was performed on lambs (123 days) to implant catheters into the pulmonary and carotid arteries and probes to measure pulmonary (PBF), carotid (CaBF) and ductus arteriosus blood flows. Lambs were delivered at 126 ± 1 days and: (1) the umbilical cord was clamped at delivery and ventilation was delayed for about 2 min (Clamp 1st; n = 6), and (2) umbilical cord clamping was delayed for 3-4 min, until after ventilation was established (Vent 1st; n = 6). All lambs were subsequently ventilated for 30 min. In Clamp 1st lambs, cord clamping rapidly (within four heartbeats), but transiently, increased pulmonary and carotid arterial pressures (by ∼30%) and CaBF (from 30.2 ± 5.6 to 40.1 ± 4.6 ml min(-1) kg(-1)), which then decreased again within 30-60 s. Following ventilation onset, these parameters rapidly increased again. In Clamp 1st lambs, cord clamping reduced heart rate (by ∼40%) and right ventricular output (RVO; from 114.6 ± 14.4 to 38.8 ± 9.7 ml min(-1) kg(-1)), which were restored by ventilation. In Vent 1st lambs, cord clamping reduced RVO from 153.5 ± 3.8 to 119.2 ± 10.6 ml min(-1) kg(-1), did not affect heart rates and resulted in stable blood flows and pressures during transition. Delaying cord clamping for 3-4 min until after ventilation is established improves cardiovascular function by increasing pulmonary blood flow before the cord is clamped. As a result, cardiac output remains stable, leading to a smoother cardiovascular transition throughout the early newborn period.

Indicators of optimal lung volume during high-frequency oscillatory ventilation in infants.

OBJECTIVES: During high-frequency oscillatory ventilation, an understanding of the relationship between lung volume and lung mechanics may help clinicians better apply ventilation. The objectives of this study were: 1) to describe the relationship between lung volume and lung function parameters during mapping of the deflation limb of the pressure-volume relationship in infants receiving high-frequency oscillatory ventilation, and 2) to determine whether these parameters might be useful in targeting an optimal volume to apply ventilation. DESIGN: Observational physiological study. SETTING: Tertiary neonatal intensive care unit in a pediatric hospital. PATIENTS: Fifteen infants receiving high-frequency oscillatory ventilation and muscle relaxants. INTERVENTIONS: The deflation limb of the pressure-volume relationship was mapped in each infant, after recruitment to total lung capacity, using stepwise airway pressure decrements. Total lung capacity and closing volume were defined by oxygenation response. MEASUREMENTS AND MAIN RESULTS: Lung volume (respiratory inductive plethysmography), oxygen saturation, transcutaneous carbon dioxide, and indicators of lung mechanics were recorded at each pressure. A distinct bell-shaped relationship between lung volume and carbon dioxide, minute ventilation, and tidal volume (both at airway opening and by inductive plethysmography) could be identified on the deflation limb, with an improvement of 21.6 mm Hg (CO2), 168 mL/sec (minute ventilation), 0.25 mL/kg (airway opening tidal volume), and 13.7% (plethysmography tidal volume) compared with total lung capacity levels. The mean (SD) optimal volumes and pressures for these parameters were significantly lower than total lung capacity, occurring at volumes between 38.6 (39.8)% and 62.8 (31.1)% of total lung capacity, and 28 (36.3)% and 41.3 (38.7)% of pressure at total lung capacity (p < 0.05; Bonferroni post-test). These coincided with the lowest pressure and volumes that maintained the oxygenation benefit of recruitment. CONCLUSIONS: Transcutaneous carbon dioxide, tidal volume, and minute ventilation may assist in refining strategies to identify optimal lung volume.

Timing of interventions in the delivery room: does reality compare with neonatal resuscitation guidelines?

OBJECTIVE: To determine the proportion of infants who had the tasks recommended in the neonatal resuscitation guidelines performed within 30 and 60 seconds of birth, and the time taken to perform each task. STUDY DESIGN: From video recordings in delivery rooms, we determined the time from birth and arrival on a resuscitation table to warm, assess heart rate (HR), attach an oximeter, and provide respiratory support for each infant. We determined the proportion of infants who had these tasks completed by 30 and 60 seconds, and the median time taken to perform each task. RESULTS: We reviewed and analyzed data from 189 infants (median gestational age, 29 weeks [IQR, 27-34 weeks]; median birth weight, 1220 g [IQR, 930-2197 g]). Twelve infants (6%) were not on the resuscitation table within 30 seconds of birth. Less than 10% of infants were placed in polyethylene bags or had their HR determined by 30 seconds. By 60 seconds, 48% were in polyethylene bags, 33% had their HR determined, 38% received respiratory support, and 60% had an oximeter attached. The median time taken to perform all tasks was greater than that recommended in the guidelines. CONCLUSION: Most newborns were not managed within the time frame recommended in resuscitation guidelines. The recommended 30- and 60-second intervals may be too short.

Fluid recovery during lung lavage in meconium aspiration syndrome.

UNLABELLED: Lung lavage using two aliquots of 15 mL/kg of dilute surfactant was performed in 30 ventilated infants with severe meconium aspiration syndrome (MAS). Mean recovery of instilled lavage fluid was 46%, with greater fluid return associated with lower mean airway pressure at 24 h and a shorter duration of respiratory support. CONCLUSION: Recovery of instilled lavage fluid is paramount in effective lung lavage in MAS and must be afforded priority in the lavage technique.

Use of ventilation/perfusion mismatch to guide individualised CPAP level selection in preterm infants: a feasibility trial.

OBJECTIVE: To measure within-subject changes in ventilation/perfusion (V'/Q') mismatch in response to a protocol of individualised nasal continuous positive airway pressure (CPAP) level selection. DESIGN: Single-arm, non-randomised, feasibility trial. SETTING: Three centres in the Children's Hospital of Philadelphia neonatal care network. PATIENTS: Twelve preterm infants of postmenstrual age 27-35 weeks, postnatal age >24 hours, and receiving a fraction of inspired oxygen (FiO2) >0.25 on CPAP of 4-7 cm H2O. INTERVENTIONS: We applied a protocol of stepwise CPAP level changes, with the overall direction and magnitude guided by individual responses in V'/Q' mismatch, as determined by the degree of right shift (kilopascals, kPa) in a non-invasive gas exchange model. Best CPAP level was defined as the final pressure level at which V'/Q' improved by more than 5%. MAIN OUTCOME MEASURES: Within-subject change in V'/Q' mismatch between baseline and best CPAP levels. RESULTS: There was a median (IQR) within-subject reduction in V'/Q' mismatch of 1.2 (0-3.2) kPa between baseline and best CPAP levels, p=0.02. Best CPAP was observed at a median (range) absolute level of 7 (5-8) cm H2O. CONCLUSIONS: Non-invasive measures of V'/Q' mismatch may be a useful approach for identifying individualised CPAP levels in preterm infants. The results of our feasibility study should be interpreted cautiously and replication in larger studies evaluating the impact of this approach on clinical outcomes is needed. TRIAL REGISTRATION NUMBER: NCT02983825.

Respiratory function monitor guidance of mask ventilation in the delivery room: a feasibility study.

OBJECTIVE: To investigate whether using a respiratory function monitor (RFM) during mask resuscitation of preterm infants reduces face mask leak and improves tidal volume (V(T)). STUDY DESIGN: Infants receiving mask resuscitation were randomized to have the display of an RFM (airway pressure, flow, and V(T) waves) either visible or masked. RESULT: Twenty-six infants had the RFM visible, and 23 had the RFM masked. The median mask leak was 37% (IQR, 21%-54%) in the visible RFM group and 54% (IQR, 37%-82%) in the masked RFM group (P = .01). Mask repositioning was done in 19 infants (73%) of the visible group and in 6 infants (26%) of the masked group (P = .001). The median expired V(T) was similar in the 2 groups. Oxygen was provided to 61% of the visible RFM group and 87% of the RFM masked group (P = .044). Continuous positive airway pressure use was greater in the visible RFM group (73% vs 43%; P = .035). Intubation in the delivery room was done in 21% of the visible group and in 57% of the masked group (P = .035). CONCLUSION: Using an RFM was associated with significantly less mask leak, more mask adjustments, and a lower rate of excessive V(T).

Effects of caffeine on renal and pulmonary function in preterm newborn lambs.

INTRODUCTION: Caffeine administration is associated with a reduction in bronchopulmonary dysplasia, assisted ventilation, patent ductus arteriosus (DA) and cerebral palsy in preterm infants, but the mechanisms are unknown. Our aim was to determine the effects of acute caffeine administration on renal and pulmonary function in preterm lambs. METHODS: Lambs were delivered by caesarean section at ~126 days of gestation and ventilated with a tidal volume of 5 ml/kg, 60 breaths/min and 5 cmH(2)O positive end-expiratory pressure. After 30 minutes, lambs received 40 mg/kg caffeine i.v (n=7) or saline (controls; n=6) over 30 minutes and were ventilated for 2 hours. RESULTS: Arterial caffeine concentrations reached 35.9 ± 7.8 mg/l. Urine output was significantly higher after caffeine treatment than in controls (5.86 ± 1.95 vs 0.76 ± 0.94 ml/kg, area under curve p=0.041). Mean heart rate was significantly higher after caffeine treatment than in controls (211 ± 8 vs 169 ± 15 beats per minute, p<0.05) and remained higher for the experimental period. DISCUSSION: Caffeine did not affect pulmonary artery or DA blood flows or other renal, respiratory or cardiovascular parameters examined. Neonatal caffeine administration increased heart rate and urine output but had little effect on pulmonary function in ventilated preterm lambs.

Prophylactic versus selective use of surfactant in preventing morbidity and mortality in preterm infants.

BACKGROUND: Surfactant therapy is effective in improving the outcome of very preterm infants. Trials have studied a wide variety of surfactant preparations used either to prevent or treat respiratory distress syndrome (RDS). In animal models, prophylactic surfactant leads to more homogeneous distribution and less evidence of lung damage. However, administration requires intubation and treatment of infants who will not go on to develop RDS. This is of particular concern with the advent of improved approaches to providing continuous distending pressure, particularly in the form of nasal continuous positive airway pressure (CPAP). OBJECTIVES: To compare the effect of prophylactic surfactant administration to surfactant treatment of established RDS in very preterm infants at risk of RDS. SEARCH METHODS: We updated the search of the Cochrane Central Register of Controlled Trials (The Cochrane Library), MEDLINE, EMBASE, CINAHL, and clinical trials.gov register in December 13, 2011. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials that compared the effects of prophylactic surfactant administration to surfactant treatment of established RDS in preterm infants at risk of RDS. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes were extracted from the reports of the clinical trials by the reviewers. Data analysis was done in accordance with the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: Eleven studies were identified that met inclusion criteria [nine without routine application of continuous positive air way pressure (CPAP) in the selective treatment group; two with routine application of CPAP in the selective treatment group]The meta-analysis of studies conducted prior to the routine application of CPAP demonstrated a decrease in the risk of air leak and neonatal mortality associated with prophylactic administration of surfactant. However, the analyses of studies that allowed for routine stabilization on CPAP demonstrated a decrease in the risk of chronic lung disease or death in infants stabilized on CPAP. When all studies were evaluated together, the benefits of prophylactic surfactant could no longer be demonstrated. AUTHORS' CONCLUSIONS: Although the early trials of prophylactic surfactant administration to infants judged to be at risk of developing RDS compared to selective use of surfactant in infants with established RDS demonstrated a decreased risk of air leak and mortality, recent large trials that reflect current practice (including greater utilization of maternal steroids and routine post delivery stabilization on CPAP) do not support these differences and demonstrate less risk of chronic lung disease or death when using early stabilization on CPAP with selective surfactant administration to infants requiring intubation.

Postnatal Cytomegalovirus Infection of Preterm and Very-low-birth-weight Infants Through Maternal Breast Milk: Does It Matter?

BACKGROUND: Postnatal infection with cytomegalovirus (CMV) in very-preterm and very-low-birth-weight infants, transmitted through breast milk (BM), is potentially associated with adverse outcomes. This study aimed to investigate the incidence and clinical significance of postnatal CMV infection in a tertiary neonatal intensive care unit. METHODS: Infants of CMV-seropositive mothers born in a neonatal intensive care unit in Melbourne, Australia, were observed for 14 weeks from birth in a prospective cohort study. Maternal BM and infant urine were tested weekly for CMV by culture and polymerase chain reaction, respectively. Clinical and laboratory data were collected and analyzed in relation to the infants' CMV infection status. RESULTS: Data from 65 infants of 56 CMV-seropositive mothers were available for analysis. Of these mothers, 88% (49/56) shed CMV in their BM. Of the 58 infants exposed to CMV-positive BM, 27 (47%) became urine polymerase chain reaction CMV-positive. There was no significant difference in gestational age, birth weight, incidence of bronchopulmonary dysplasia, or necrotizing enterocolitis between the CMV-positive and CMV-negative groups. However, CMV-positive infants had a longer length of hospital stay and more episodes of prolonged neutropenia. Of the CMV-positive infants, 30% (8/27) remained asymptomatic, 48% (13/27) had symptoms categorized as mild and 22% (6/27) as severe. CONCLUSIONS: About half of preterm and very-low-birth-weight infants exposed to CMV-positive BM become infected, and a fifth develop significant clinical symptoms. Future studies should address the maternal and neonatal factors that determine the risk of mother-to-infant CMV transmission, as well as those leading to clinical deterioration and long-term sequelae.

Nasal CPAP or intubation at birth for very preterm infants.

BACKGROUND: Bronchopulmonary dysplasia is associated with ventilation and oxygen treatment. This randomized trial investigated whether nasal continuous positive airway pressure (CPAP), rather than intubation and ventilation, shortly after birth would reduce the rate of death or bronchopulmonary dysplasia in very preterm infants. METHODS: We randomly assigned 610 infants who were born at 25-to-28-weeks' gestation to CPAP or intubation and ventilation at 5 minutes after birth. We assessed outcomes at 28 days of age, at 36 weeks' gestational age, and before discharge. RESULTS: At 36 weeks' gestational age, 33.9% of 307 infants who were assigned to receive CPAP had died or had bronchopulmonary dysplasia, as compared with 38.9% of 303 infants who were assigned to receive intubation (odds ratio favoring CPAP, 0.80; 95% confidence interval [CI], 0.58 to 1.12; P=0.19). At 28 days, there was a lower risk of death or need for oxygen therapy in the CPAP group than in the intubation group (odds ratio, 0.63; 95% CI, 0.46 to 0.88; P=0.006). There was little difference in overall mortality. In the CPAP group, 46% of infants were intubated during the first 5 days, and the use of surfactant was halved. The incidence of pneumothorax was 9% in the CPAP group, as compared with 3% in the intubation group (P<0.001). There were no other serious adverse events. The CPAP group had fewer days of ventilation. CONCLUSIONS: In infants born at 25-to-28-weeks' gestation, early nasal CPAP did not significantly reduce the rate of death or bronchopulmonary dysplasia, as compared with intubation. Even though the CPAP group had more incidences of pneumothorax, fewer infants received oxygen at 28 days, and they had fewer days of ventilation. (Australian New Zealand Clinical Trials Registry number, 12606000258550.).

Identification of pneumothorax in very preterm infants.

OBJECTIVE: To compare respiratory and other morbidities between very preterm infants with and without a pneumothorax and to determine whether infants at higher risk of pneumothorax can be identified early in their course. STUDY DESIGN: Preterm infants at 23 to 28 weeks' gestation with pneumothorax were compared with matched control subjects. Demographic and clinical data from birth through the first 72 hours were compared. RESULTS: Sixty-two (9.2%) of 675 infants had pneumothorax. There were no significant differences in the baseline maternal and infant characteristics. Mortality was significantly higher in the pneumothorax group (43%) versus control subjects (13%). There was no significant difference in continuous positive airway pressure or surfactant treatment or rates of intraventricular hemorrhage or bronchopulmonary dysplasia. Infants treated with early continuous positive airway pressure in the delivery room typically had pneumothorax on day 2 of life. Those who had pneumothorax had higher inspired fraction of oxygen before its diagnosis and over the first 12 hours of life than did control subjects. CONCLUSIONS: Pneumothorax is associated with increased mortality and with severity of lung disease in the first day of life. It may be possible to identify babies at highest risk of pneumothorax on the basis of inspired fraction of oxygen in the first 12 hours of life.

Oxygenation with T-piece versus self-inflating bag for ventilation of extremely preterm infants at birth: a randomized controlled trial.

OBJECTIVE: To investigate whether infants < 29 weeks gestation who receive positive pressure ventilation (PPV) immediately after birth with a T-piece have higher oxygen saturation (SpO2) measurements at 5 minutes than infants ventilated with a self inflating bag (SIB). STUDY DESIGN: Randomized, controlled trial of T-piece or SIB ventilation in which SpO2 was recorded immediately after birth from the right hand/wrist with a Masimo Radical pulse oximeter, set at 2-second averaging and maximum sensitivity. All resuscitations started with air. RESULTS: Forty-one infants received PPV with a T-piece and 39 infants received PPV with a SIB. At 5 minutes after birth, there was no significant difference between the median (interquartile range) SpO2 in the T-piece and SIB groups (61% [13% to 72%] versus 55% [42% to 67%]; P = .27). More infants in the T-piece group received oxygen during delivery room resuscitation (41 [100%] versus 35 [90%], P = .04). There was no difference in the groups in the use of continuous positive airway pressure, endotracheal intubation, or administration of surfactant in the delivery room. CONCLUSION: There was no significant difference in SpO2 at 5 minutes after birth in infants < 29 weeks gestation given PPV with a T-piece or a SIB as used in this study.